This invention relates to Human Growth Factors (HGFs) and, more particularly, to the sterilization of therapeutic compositions and surgical articles such as ligatures, hemostatic clips, prosthetic implants, etc., containing one or more HGFs in which ethylene oxide gas is employed as the sterilizant.
HGFs are polypeptides which are known to beneficially affect the wound healing process. See, e.g., Brown et al., "Acceleration of Tensile Strength of Incisions Treated with EGF and TGF-beta", Ann. Surg., pp 788 et seq (Dec. 1988) and Barbul, et al., eds., "Growth Factors and Other Aspects of Wound Healing/Biological and Clinical Implications", Proceedings Of the Second International Symposium on Tissue Repair, Tarpon Springs, Fla., May 13-17, 1987 (Alan R. Liss, Inc., New York). Individual HGFs include Human Epidermal Growth Factor (hEGF), Transforming Growth Factor-Beta (TGF-beta), Insulin-like Growth Factor (IGF), Platelet-derived Growth Factor (PDGF) and Fibroblast Growth Factor (FGF).
HGFs are known to be fairly susceptible to degradation. This tendency presents practical difficulties when it is desired to effect their sterilization without, however, negatively affecting their biopotency to an excessive degree. Like most proteinaceous materials, HGFs are heat labile thus ruling out thermal treatments as practical ways to achieve their sterilization. While the use of cold sterilization techniques employing ethylene oxide gaseous compositions has been known for years, the bactericidal action of ethylene oxide is thought to involve a chemical alteration of bacterial proteins, namely through ethoxylation, which accounts for the resulting sterilization. Apparently aware of this, workers in the field have thus far refrained from even investigating the use of ethylene oxide for the sterilization of HGFs.
To date, the prior art has provided little guidance to those concerned with the problem of achieving a practical and effective procedure for sterilizing HGFs. U.S. Pat. No. 3,917,824 indicates that the use of a sterilizing membrane filtration system, e.g., a 0.22 m.mu. Millipore.RTM. filter, a procedure which avoids elevated temperatures and highly reactive chemical sterilizants, is effective for the sterilization of EGFs. However, such a procedure can be impractical for practice on all but a laboratory scale and in any event, cannot be practiced after the EGF has been formulated into a dosage form or has been applied to a solid substrate, e.g., a suture.